Preoperative-induced mild hypothermia attenuates neuronal damage in a rat subdural hematoma model.

Post-traumatic hypothermia has been effective for traumatic brain injury in the laboratory setting. However, hypothermia has not shown efficacy in clinical trials. With the results of a recent clinical trial, we hypothesized that hypothermia might reduce neuronal damage in acute subdural hematoma (ASDH) by blunting the effects of reperfusion injury. Twenty rats were induced with ASDH and placed into one of four groups. The normothermia group was maintained at 37 °C throughout. In the early hypothermia group, brain temperature was reduced to 33 °C 30 min prior to craniotomy. In the late hypothermia group, brain temperature was lowered to 33 °C 30 min after decompression. The sham group had no ASDH and underwent only craniotomy with normothermia. For estimation of glial and neuronal cell damage, we analyzed serum and microdialysate (using a 100kD probe) concentrations of: glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl--terminal hydrolase -L1 (UCH-L1). Hypothermia induced early significantly reduced the concentration of MD UCH-L1. In conclusion, hypothermia induced early may reduce neuronal cell damage in the reperfusion injury, which was induced after ASDH removal. MD UCH-L1 seems like a good -candidate for a sensitive microdialysate biomarker for -neuronal injury and outcome.

Serum levels of ubiquitin C-terminal hydrolase distinguish mild traumatic brain injury from trauma controls and are elevated in mild and moderate traumatic brain injury patients with intracranial lesions and neurosurgical intervention.

BACKGROUND: This study compared early serum levels of ubiquitin C-terminal hydrolase (UCH-L1) from patients with mild and moderate traumatic brain injury (TBI) with uninjured and injured controls and examined their association with traumatic intracranial lesions on computed tomography (CT) scan (CT positive) and the need for neurosurgical intervention (NSI). METHODS: This prospective cohort study enrolled adult patients presenting to three tertiary care Level I trauma centers after blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale (GCS) score 9 to 15. Control groups included normal uninjured controls and nonhead injured trauma controls presenting to the emergency department with orthopedic injuries or motor vehicle crash without TBI. Blood samples were obtained in all trauma patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for UCH-L1 (ng/mL ± standard error of the mean). RESULTS: There were 295 patients enrolled, 96 TBI patients (86 with GCS score 13-15 and 10 with GCS score 9-12), and 199 controls (176 uninjured, 16 motor vehicle crash controls, and 7 orthopedic controls). The AUC for distinguishing TBI from uninjured controls was 0.87 (95% confidence interval [CI], 0.82-0.92) and for distinguishing those TBIs with GCS score 15 from controls was AUC 0.87 (95% CI, 0.81-0.93). Mean UCH-L1 levels in patients with CT negative versus CT positive were 0.620 (± 0.254) and 1.618 (± 0.474), respectively (p < 0.001), and the AUC was 0.73 (95% CI, 0.62-0.84). For patients without and with NSI, levels were 0.627 (0.218) versus 2.568 (0.854; p < 0.001), and the AUC was 0.85 (95% CI, 0.76-0.94). CONCLUSION: UCH-L1 is detectable in serum within an hour of injury and is associated with measures of injury severity including the GCS score, CT lesions, and NSI. Further study is required to validate these findings before clinical application. LEVEL OF EVIDENCE: II, prognostic study.

Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention.

STUDY OBJECTIVE: This study examines whether serum levels of glial fibrillary acidic protein breakdown products (GFAP-BDP) are elevated in patients with mild and moderate traumatic brain injury compared with controls and whether they are associated with traumatic intracranial lesions on computed tomography (CT) scan (positive CT result) and with having a neurosurgical intervention. METHODS: This prospective cohort study enrolled adult patients presenting to 3 Level I trauma centers after blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale (GCS) score of 9 to 15. Control groups included normal uninjured controls and trauma controls presenting to the emergency department with orthopedic injuries or a motor vehicle crash without traumatic brain injury. Blood samples were obtained in all patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for GFAP-BDP (nanograms/milliliter). RESULTS: Of the 307 patients enrolled, 108 were patients with traumatic brain injury (97 with GCS score 13 to 15 and 11 with GCS score 9 to 12) and 199 were controls (176 normal controls and 16 motor vehicle crash controls and 7 orthopedic controls). Receiver operating characteristic curves demonstrated that early GFAP-BDP levels were able to distinguish patients with traumatic brain injury from uninjured controls with an area under the curve of 0.90 (95% confidence interval [CI] 0.86 to 0.94) and differentiated traumatic brain injury with a GCS score of 15 with an area under the curve of 0.88 (95% CI 0.82 to 0.93). Thirty-two patients with traumatic brain injury (30%) had lesions on CT. The area under these curves for discriminating patients with CT lesions versus those without CT lesions was 0.79 (95% CI 0.69 to 0.89). Moreover, the receiver operating characteristic curve for distinguishing neurosurgical intervention from no neurosurgical intervention yielded an area under the curve of 0.87 (95% CI 0.77 to 0.96). CONCLUSION: GFAP-BDP is detectable in serum within an hour of injury and is associated with measures of injury severity, including the GCS score, CT lesions, and neurosurgical intervention. Further study is required to validate these findings before clinical application.

Ubiquitin C-terminal hydrolase-L1 as a biomarker for ischemic and traumatic brain injury in rats.

Ubiquitin C-terminal hydrolase-L1 (UCH-L1), also called neuronal-specific protein gene product 9.5, is a highly abundant protein in the neuronal cell body and has been identified as a possible biomarker on the basis of a recent proteomic study. In this study, we examined whether UCH-L1 was significantly elevated in cerebrospinal fluid (CSF) following controlled cortical impact (CCI) and middle cerebral artery occlusion (MCAO; model of ischemic stroke) in rats. Quantitative immunoblots of rat CSF revealed a dramatic elevation of UCH-L1 protein 48 h after severe CCI and as early as 6 h after mild (30 min) and severe (2 h) MCAO. A sandwich enzyme-linked immunosorbent assay constructed to measure UCH-L1 sensitively and quantitatively showed that CSF UCH-L1 levels were significantly elevated as early as 2 h and up to 48 h after CCI. Similarly, UCH-L1 levels were also significantly elevated in CSF from 6 to 72 h after 30 min of MCAO and from 6 to 120 h after 2 h of MCAO. These data are comparable to the profile of the calpain-produced alphaII-spectrin breakdown product of 145 kDa biomarker. Importantly, serum UCH-L1 biomarker levels were also significantly elevated after CCI. Similarly, serum UCH-L1 levels in the 2-h MCAO group were significantly higher than those in the 30-min group. Taken together, these data from two rat models of acute brain injury strongly suggest that UCH-L1 is a candidate brain injury biomarker detectable in biofluid compartments (CSF and serum).